Radiotherapy Unit, Meldola
Neoplasie del polmone e trattamenti combinati
Donatella Arpa
Neoplasie del polmone e trattamenti combinati
CHEMIOTERAPIA RADIOTERAPIA CHIRURGIA
IMMUNOTERAPIA
Definitive therapy for locally advanced NSCLC, generally combined with chemotherapy.
Definitive therapy for early stage .
Preoperative or postoperative therapy for selected patients treated with surgery.
Therapy for limited recurrence and metastases.
Neoplasie del polmone e trattamenti
combinati
Non-Small- Cell Lung Cancer
Unresectable IIIA-IIIB
Resectable IIIA
Locally Advanced Non-Small- Cell Lung Cancer
Unresectable IIIA –IIIB NSCLC
Progression-free survival was significantly longer with durvalumab than with placebo.
The secondary end points also favored durvalumab, and safety was similar between the groups.
(Funded by AstraZeneca; PACIFIC ClinicalTrials.gov
number, NCT02125461
.)Optimal RT dose:RTOG 0617
a median survival of 28 months.
MS continues to range from 10 to 26 mo with a 5- year survival rate of less than 25%.
Previous work has demonstrated that
Lengthening treatment time beyond 6 weeks has a negative impact on overall survival,
likely due to accelerated repopulation of tumor cells .
Optimal RT dose…….
IS IT ENOUGH ???
Hyperfractionation
hypofractionation
Optimal RT dose…….
the analysis of Machtay demonstrated a moderate
linear relationship between lesional BED and overall
survival: for every 1 Gy increase in BED, there was
an absolute overall survival benefit ranging from
0.36% to 0.7%.
Non-Small- Cell Lung Cancer
Unresectable IIIA-IIIB
Resectable IIIA
Definitive therapy for locally advanced NSCLC, generally combined with chemotherapy.
Definitive therapy for early stage .
Preoperative or postoperative therapy for selected patients treated with surgery.
Therapy for limited recurrence and metastases.
Neoplasie del polmone e trattamenti
combinati
Despite having complete resection and adjuvant chemotherapy , up to 40% of
resectable stage IIIA patients experience local tumor recurrence.
In order to improve local tumor control and survival, post-operative radiotherapy (PORT) has long been utilized to intensify local therapy.
Postoperative therapy (PORT)
Postoperative therapy (PORT)
Adverse effect on survival by increasing the relative risk of death by 21%,
translating to a 7%
reduction in 2-year OS from 55% to 48%.
Subgroup analysis
indicated a detriment in OS for patients with stage I/II N0-1 due to excess of toxicity from PORT.
PORT for stage III-N2
disease trended toward, but did not reach, a significant survival benefit.
Is it true?
A significant flaw of the PORT Meta-analysis was the inclusion of historical series with patients
treatments utilizing antiquated techniques
that were potentially more toxic than modern radiation delivery with image
guidance, respiratory motion assessment, and higher dose conformality.
Lally BE.Postoperative radiotherapy for stage II or III nonsmall-cell lung cancer using the surveillance,
epidemiology, and end results database. J Clin Oncol 2006
Robinson CG. Postoperative radiotherapy for pathologic N2 non-small-cell lung cancer treated with adjuvant
chemotherapy: a review of the National Cancer Data Base.
J Clin Oncol 2015
Douillard JY Impact of postoperative radiation therapy on survival in patients with complete resection and stage I, II, or IIIA non-smallcell lung cancer treated with adjuvant chemotherapy: the adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial. Int J Radiat Oncol Biol Phys 2008,
Postoperative therapy (PORT)
Postoperative therapy (PORT)
N2
In case of R1 resection (positive resection margin, chest wall),PORT should be considered
In completely resected early-stage NSCLC is not recommended
In case both ChT and RT are administered post- surgery, RT should be administered after ChT
Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Annals of Oncology 28 (Supplement 4): iv1–iv21, 2017
Preoperative therapy
Therapeutic management options for stage III non-small cell lung cancerWorld J Clin Oncol 2017 February 10; 8(1): 1-20 ISSN 2218-4333
Surgical resection may not improve treatment
outcomes compared to definitive
radiotherapy. Within the context that
radiotherapy leads to lower morbidity and
mortality compared to surgery, definitive
chemoradiation is a reasonable treatment
option for patients with stage IIIA-N2
disease.
5-year OS and MS were not improved with the induction chemoradiation.
Five-year PFS was significantly higher under the intervention arm (22.4%) compared to
chemoradiation arm (11.1%).
Relatively high treatment-related deaths were
observed in the trimodality arm (7.9%) compared
to definitive chemoradiation arm (2.1%).
No significant differences were found for either
OS or PFS between the two groups, thus making
either strategies acceptable for resectable stage
IIIA, and select inoperable IIIA or IIIB patients.
RT
Oligoprogressive disease
Oligometastatic disease
Neoplasie del polmone e trattamenti
combinati
Oligoprogressive and oligometastatic disease
Oligometastatic state : metastatic disease is
present at a limited number of anatomic sites is being increasingly recognized.
Oligoprogressive state: disease progression at a limited number of anatomic sites, with continued response or stable disease at other sites of disease.
Such an oligoprogressive state is best described in patients with NSCLC treated with molecular
targeted therapy.
Oligoprogressive and oligometastatic
disease
Radiotherapy :“Therapeutic Ratio”
The concept of therapeutic ratio is best illustrated graphically, by making a direct comparison of dose-response curves for both tumor control and normal tissue complication rates plotted as a function of dose.
Precise targeting
Imaging
Imaging
Contouring
Treatment volume
Icru 50, 62
Intrafraction modifications
Interfraction modifications
IGRT
Our experience NSLC
25 Gy in 5 frazioni su T ed N 15 Gy in 3 frazioni
(con una disomogeneità interna sino a 37.5 Gy)
30 Gy in 5 frazioni su T
25gy in 5 frazioni su N
Ipofrazionamento della dose
Split course
I ciclo RT: 30 Gy in 5 frazioniT e 25 Gy in 5 frazioni N (24-30/05/16)
II ciclo RT: 15 Gy in 3 frazioni 7-11/07/16
Induction CT Radiotherapy Consolidation CT CDDP
75 mg/mq (1,21)
DOCETAXEL
75 mg/mq (1,21) (2 cycles)
Accelerated Hypofractio nated RT
(From 15th to 19th)
CDDP
75 mg/mq (1,21)
DOCETAXEL
75 mg/mq (1,21) (2 cycles)
FBS and/or TBNA PET CT scan Biopsy
Program protocol
T 30 Gy/5 fractions up to 40 Gy
N 25 Gy/5 fractions up to 37.5 Gy
cT4 cN2 M0 squamous carcinoma
ycTx ycN0 M0
cT4 cN3 M0 adenocarcinoma
ycTx ycN0 M0
30/01/14 FBS ; ADENOK ALK TRASLOCATO
RT 2009, PROTOCOLLO IRST
ycTx ycN0 M0
Dal 29/03/2014- 2/04/14 25 gy in 5 frazioni con dismogeneità 31.25 Gy
PD aprile 2015… avvio di crizotinib
ypT0 ypN0(0/34) ypMx
cT4 cN3 M0 squamous carcinoma cT4 cN3 M0 adenocarcinoma
ycT0 ycN0 yMx
cT4 cN3 cM0 adenocarcinoma
ycT4 ycN0 cM0 adenocarcinoma
cT3cN2 cM0 large cell carcinoma
ycT0 ycN0 cM1 large cell carcinoma
Grade (No. = 19)
1 2 3-4
Toxicity (WHO/RTOG) No. % No. % No. %
Neutropenia - - 2 12.5 11 68.8
Leucopenia - - 2 12.5 8 50.1
Anemia - - 2 12.5 - -
Creatinine - - 3 18.8 - -
Fatigue - - 2 12.5 1 6.3
Mucositis - - 1 6.3 - -
Overall Chemoteraphy and Radiotherapy Toxicity
No cases of acute pneumonia or esophagitis (G3/4)were observed
Overall Survival
(median follow-up : 23 months, range 2-42)
2012/10/14
0.00 0.20 0.40 0.60 0.80 1.00
OS
0 6 12 18 24 30
months
Median OS: 27.0 months (95% CI 9.6-not reached)
Pts at risk 23 20 11 10 6 4
Local Progression-Free Survival
2012/09/14
Metastasis-Free Survival
0.00 0.20 0.40 0.60 0.80 1.00
Relgional Free Survival
0 6 12 18 24 30
months
Median LPFS: 19.8 months (95% CI 9.7-not reached)
Pts at risk 17 16 10 7 3 2
0.00 0.20 0.40 0.60 0.80 1.00
Metastasis Free Survival
0 6 12 18
months
Median MFS: 9.7 months (95% CI 5.8-not reached)
Pts at risk 17 13 5 4
Local Progression Free Survival
